This research is to determine the role of granulocytes in thrombotic disease. It has already been determined that granulocytes can develop thromboplastic activity, that they are specifically located in thrombi adjacent to the fibrin, and that they are required for endotoxin induced intravascular coagulation and the generalized Shwartzman reaction. Work on this project has also demonstrated that production of thromboplastin by leukocytes requires protein synthesis and by interfering with this protein synthesis in an experimental model, one can prevent the generalized Shwartzman reaction. We have shown that minimal trauma to a dog vein leads to the accumulation of large numbers of granulocytes on the vein wall which then produce thromboplastin and sometimes thrombosis. We are now investigating a similar lesion of leukocyte adhesion and thrombosis induced by norepinephrine infusion. We will study the role of granulocytes in producing thrombi by this method, by inducing agranulocytosis in dogs and then attempting to induce thrombosis. We will also study in vitro adhesion of granulocytes to glass and cultured endothelial cell monolayers. The characteristics of the adherent cells and the effects of thrombocytopenia, anticoagulation and pharmacologic manipulation will be studied in vivo and in vitro.